%0 Journal Article
%T Artificial Specific Binders Directly Recovered from Chemically Modified Nucleic Acid Libraries
%A Yuuya Kasahara
%A Masayasu Kuwahara
%J Journal of Nucleic Acids
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/156482
%X Specific binders comprised of nucleic acids, that is, RNA/DNA aptamers, are attractive functional biopolymers owing to their potential broad application in medicine, food hygiene, environmental analysis, and biological research. Despite the large number of reports on selection of natural DNA/RNA aptamers, there are not many examples of direct screening of chemically modified nucleic acid aptamers. This is because of (i) the inferior efficiency and accuracy of polymerase reactions involving transcription/reverse-transcription of modified nucleotides compared with those of natural nucleotides, (ii) technical difficulties and additional time and effort required when using modified nucleic acid libraries, and (iii) ambiguous efficacies of chemical modifications in binding properties until recently; in contrast, the effects of chemical modifications on biostability are well studied using various nucleotide analogs. Although reports on the direct screening of a modified nucleic acid library remain in the minority, chemical modifications would be essential when further functional expansion of nucleic acid aptamers, in particular for medical and biological uses, is considered. This paper focuses on enzymatic production of chemically modified nucleic acids and their application to random screenings. In addition, recent advances and possible future research are also described. 1. Introduction RNA/DNA aptamers, which are specific for a broad spectrum of targets, can be artificially created by systematic evolution of ligands by exponential enrichment (SELEX) methods [1, 2]. Large-scale chemical synthesis of RNA/DNA aptamers is possible, and synthesizing them is less expensive than producing antibodies; therefore, they have been considered as alternatives to therapeutic antibodies. Although RNA/DNA aptamers do not cause antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), their specific binding abilities are expected to neutralize actions on the target and relieve symptoms. Indeed, the first example of an aptamer drug, ¡°Macugen (pegaptanib sodium injection)¡± is being used for age-related macular degeneration (AMD) therapy [3]. Pegaptanib is a RNA-based aptamer that involves 2¡ä-fluoropyrimidine nucleotides (U, C) and 2¡ä-methoxy purine nucleotides (A, G) to remain intact under physiological conditions. In addition, a branched polyethylene glycol strand (40£¿kDa) and 3¡ä-thymidylic acid are introduced at its 5¡ä and 3¡ä ends, respectively. The 5¡ä-end modification is known to prolong circulation time in vivo as well as to enhance
%U http://www.hindawi.com/journals/jna/2012/156482/